Requirement of the Ca2+ channel β2 subunit for sympathetic PKA phosphorylation

Manabu Murakami, Feng Xu, Takayoshi Ohba, Takeshi Kobayashi, Yoshiro Inoue, Agnieszka M. Murakami, Ichiro Miyoshi, Kyoichi Ono, Noritsugu Tohse

Research output: Contribution to journalArticlepeer-review

Abstract

Facilitation of cardiac function in response to signals from the sympathetic nervous system is initiated by the phosphorylation of L-type voltage-dependent Ca2+ channels (VDCCs) by protein kinase A (PKA), which in turn is activated by β-adrenoceptors. Among the five subunits (α1, β, α2/δ, and γ) of VDCCs, the α1 subunit and the family of β subunits are substrates for PKA-catalyzed phosphorylation; however, the subunit responsible for β-adrenergic augmentation of Ca2+ channel function has yet to be specifically identified. Here we show that the VDCC β2 subunit is required for PKA phosphorylation upon sympathetic acceleration. In mice with β2 subunit-null mutations, cardiac muscle contraction in response to isoproterenol was reduced and there was no significant increase in Ca2+ channel currents upon PKA-dependent phosphorylation. These findings indicate that within the sympathetic nervous system the β2 subunit of VDCCs is required for physiological PKA-dependent channel phosphorylation.

Original languageEnglish
Pages (from-to)253-261
Number of pages9
JournalJournal of Pharmacological Sciences
Volume145
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • Calcium
  • Channel
  • Mouse
  • Phosphorylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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